Polyoxyethylated castor oils or Cremophor(s) are nonionic surfactants used to solubilize or disperse perfumes, cosmetics, vitamins, pharmaceuticals, pesticides and paints, in aqueous media. Ability of polyoxethylated castor oils to solubilize so many different substances stems from their unique chemical structures presenting hydrophilic polymer chains attached in the center of fatty acid alkyl chains in castor oil triglycerides. Main component of castor oil is triricinolein or triglyceride of ricinoleic acid which contains free hydroxyl group at C12 position in each of the three fatty acid alkyl chains in its structure. Polymerization of ethylene oxide is initiated from these hydroxyl groups and surfactants with a range of hydrophilic-lipophilic balance values (HLB values) are prepared.
Polyoxyethylated castor oils however are known to cause hypersensitivity reactions in pharmaceutical formulations such as of paclitaxel (Cremophor EL containing paclitaxel-induced anaphylaxis: a call to action, Irizarry, L. D. et al Community Oncology, 6(3) 132-134 (2009)). Additionally, castor oil harvesting poses a human health risk due to the formation of side product ricin which is a potent toxin. Edible oils are much safer and cheaper alternative to castor oil as raw material for preparation of surfactants. Therefore it is desirable to prepare surfactants that are safer, equivalent substitute for polyoxyethylated castor oils but are derived from edible oils. Besides, Cremophor EL is a complex mixture of many surfactant species formed by reaction of castor oil triglycerides and ethylene oxide polymers (Separation and first structure elucidation of Cremophor-EL components by hyphenated capillary electrophoresis and delayed extraction-matrix assisted laser desorption/ionization time of flight mass spectrometry, Meyer, T. et al Electrophoresis 23(7-8) 1053-1062 (2002)). In pharmaceutical preparations, well-defined structure of surfactant is highly desirable. Thus, there is need of surfactants with well-defined structure and controllable molecular weight and functionality of attached polyoxyethylene chains. Therefore, it is desirable to devise a chemistry that allows strict control on the molecular weight and functionality of polyoxyethylene chains attached to a surfactant formed by oil.
However, edible oils do not contain reactive hydroxyl group in the center of fatty acid alkyl chains in their structures which could be utilized to attach polymer chains as in the case of polyoxyethylated castor oil. Only carbon-carbon double bonds are present in the center of fatty acid alkyl chains in unsaturated edible oils. Epoxidation of double bonds in unsaturated edible oils is most commonly used to attempt any chemical modification of the oil.
For example U.S. Pat. No. 5,442,082 describe preparation of surfactants by reacting epoxidized soybean oil with glycerol followed by polymerization of ethylene oxide initiated by the newly attached hydroxyl groups to the modified soybean oil. Similarly, U.S. Pat. No. 6,057,375 describe preparation of surfactants by reacting epoxidized soybean oil with carboxylic acids to open the epoxide ring followed by polymerization of ethylene oxide initiated by free hydroxyl groups in the modified oil made available by epoxide ring opening. Such reactions are typically carried out at high temperatures because of poor reactivity of hydroxyl and carboxyl groups towards opening of epoxide rings in the oil. At high temperatures, triacylglycerol structures of oils are susceptible to transesterification reactions with alcohols thus resultant product is a complex mixture of different surfactant species. Also, high temperature and plurality of initiator sites involved generally result in complex mixture of ethylene oxide polymers and surfactants thereof.